It is proposed to develop a general method for the efficient computation of isotope effects on specific biochemical reactions. This method is to be incorporated into a computer program which will allow the general investigator to carry out meaningful calculations requiring little more input than the structural information specified in conventional transition state models. Although the basic theoretical apparatus for isotope rate effect calculations is well-known, very few reactions have been adequately modelled; for example, in only a few of the most carefully studied reactions have realistic reaction coordinate motions been considered. There are three general reasons for this gap between theory and practice: (1) the relative complexity of the mathematical techniques, (2) the inadequacy of the available information on molecular force constants and (3) the inadequate exploitation of general chemical relationships such as those exemplified in Johnston's BEBO method. Since isotope effects constitute one of the most generally applicable techniques for the investigation of biochemical mechanisms, it is important that the general investigator have available an easily usable theoretical apparatus to interpret experimental isotope effects and to make predictions. We propose to provide this. The growing body of vibrational spectroscopic information on organic compounds can be analyzed to give useful transferrable force constants. The mathematical manipulations and the general chemical relationships can be incorporated into an interactive computer program. The program can be made available through the Quantum Chemistry Program Exchange or possibly through telex type links which could also allow collaboration and/or consultation among research groups.